Elsevier

Sleep Medicine Reviews

Volume 38, April 2018, Pages 39-49
Sleep Medicine Reviews

Clinical Review
Cognitive deficits in obstructive sleep apnea: Insights from a meta-review and comparison with deficits observed in COPD, insomnia, and sleep deprivation

https://doi.org/10.1016/j.smrv.2017.03.005Get rights and content

Summary

Obstructive sleep apnea (OSA) is a nocturnal breathing disorder that is associated with cognitive impairment. The primary determinants of cognitive deficits in OSA are thought to be sleep disruption and blood gas abnormalities. Cognitive impairment is also seen in other disorders that are characterised primarily by sleep disturbance (e.g., sleep restriction/deprivation, insomnia) or hypoxia/hypercarbia (e.g., chronic obstructive pulmonary disease (COPD)). Assessment of the cognitive deficits observed in these other disorders could help better define the mechanisms underlying cognitive deficits in OSA. This study utilised meta-review methodology to examine the findings from systematic reviews and meta-analyses of the effects of untreated OSA, COPD, insomnia, and sleep deprivation on cognitive function in adults, compared with norms or controls. Eighteen papers met inclusion criteria: seven in OSA, two in insomnia, five in COPD, and four in sleep deprivation. OSA and COPD were both accompanied by deficits in attention, memory, executive function, psychomotor function, and language abilities, suggesting that hypoxia/hypercarbia may be an important determinant of deficits in these domains in OSA. Both OSA and sleep deprivation studies were accompanied by deficits in attention and memory, suggesting that short-term sleep disturbance in OSA may contribute to deficits in these domains. Visuospatial deficits were unique to OSA, suggesting the contribution of a mechanism other than sleep disturbance and hypoxia/hypercarbia to this problem. Our findings suggest that the cognitive deficits associated with untreated OSA are multidimensional, with different physiological disturbances responsible for differing cognitive problems.

Introduction

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterised by repetitive episodes of partial (hypopneas) or complete (apneas) obstruction of the pharyngeal airway. Varying degrees of hypoxia and hypercarbia accompany these events, which are usually terminated by brief arousals from sleep. The repetitive nature of apneas and hypopneas results in fragmented sleep and disturbed sleep architecture. OSA is estimated to occur in 9% of middle-aged women, and 27% of middle-aged men [1], and these figures are rising with population ageing and weight gain [2], with projected costs of $US3.4-6.9B per annum [3], two-to three-fold increased risk of motor vehicle accidents [4], mood disruption, occupational injuries and absenteeism, and greater risk of relationship discord, reduced quality of life [5], and impaired cognition [6].

The profile of cognitive deficits in OSA has been summarised in several systematic reviews and meta-analyses [7], ∗[8], ∗[9], [10], ∗[11] with a recent meta-review of these studies concluding that individuals with OSA exhibit deficits in the cognitive domains of attention/vigilance, delayed long-term visual and verbal memory, visuospatial/constructional abilities, and executive functions. Language ability and psychomotor function appear to be spared [6].

While the profile of cognitive deficits in OSA is becoming clearer, the underlying mechanisms that impair cognition in OSA remain uncertain. The dominant theoretical framework of cognitive harm focuses on hypoxia, hypercarbia, and sleep disruption [12], [13]. However, evidence for these mechanisms remains equivocal [14]. For example, in the most thorough review of relationships between indices of nocturnal symptoms and cognitive deficits in OSA, to date, Aloia et al. [14] found no consistent relationship between degree of cognitive impairment reported and the severity of sleep disturbance or hypoxia.

It is likely that some of the ambiguity in these relationships stems from difficulty in separating the contribution of sleep disturbance and blood gas abnormalities, as these events often co-occur in OSA. To date, just one study [15] has used a statistical approach to separate the relative impact of hypoxia and sleep disruption on cognition in OSA, and none have considered hypercarbia separately. Olaithe et al. [15] applied structural equation modelling (SEM) to partition hypoxia from sleep disruption, and used this model to examine the relationship between these mechanisms of harm and cognitive deficits in an OSA sample. They found that sleep fragmentation, but not hypoxia, was associated with deficits in attention and executive function. However, due to the co-occurrence of apneas/hypopneas (hypoxic events) and arousals (sleep disrupting events), and the use of traditional measures of respiratory and sleep disturbances, which count the number of events, this statistical model maintained a high degree of association between sleep disruption and hypoxic events (r = 0.70). As such, this statistical approach was unable completely to separate effects of hypoxia from sleep disruption using traditional indices of nocturnal symptoms.

An alternative approach is to compare OSA with conditions where just one of the proposed mechanisms of harm predominates, using meta-review. There is marked heterogeneity in the measures used to quantify disturbances of cognition, sleep and blood gas indices, and studies have often involved relatively small sample sizes. Meta-review of meta-analytic and/or systematic reviews represents one way to address this ambiguity in both mechanism and measurement, by aggregating performance across many tasks, indices, participant numbers [16], and conditions.

Better to understand the mechanisms of cognitive deficits in OSA, we used meta-review techniques to compare the cognitive profiles of disorders that differentially disturb sleep architecture, and/or cause hypoxia and hypercarbia. Such an approach allows the overlapping influences of blood gas disturbances and sleep disruption seen in OSA to be teased apart. Identification of shared or unique cognitive deficits occurring between OSA and exemplar disorders may shed light on the underlying mechanisms of cognitive harm in OSA. Aspects of such a comparative, disease-based approach have been used in three previous studies. In 1995, Roher et al. [17] compared the cognitive function of individuals with OSA and chronic obstructive pulmonary disease (COPD), positing that because airflow limitation was a key component of both conditions any differences between the groups could be attributed to sleep disruption. The study reported that individuals with OSA were more impaired than those with COPD on sustained attention tasks. In 2001, Fulda and Shulz [18] examined differences in cognition between individuals with OSA and those with insomnia, demonstrating that individuals with OSA exhibit greater cognitive deficits than those with insomnia on tasks assessing driving ability and attention. Finally, in 2015, a narrative review by Andreou et al. [19] reported many similarities in the cognitive profiles of COPD and OSA, leading the authors to conclude that the underlying mechanisms of cognitive harm were similar.

The present study extends these earlier investigations by defining and comparing the effects of OSA (characterised by hypoxia, hypercarbia, short and chronic sleep disruption), COPD (characterised by hypoxia and hypercarbia), insomnia (characterised by chronic sleep disruption) and experimental studies of sleep deprivation (characterised by short-term sleep disruption) on cognition. COPD and OSA represent two of the most common respiratory conditions. Both increase in prevalence with age, are characterised by airflow limitation, and are accompanied by hypoxia and hypercarbia [1], [20]. In contrast to COPD, but similarly to OSA, individuals with insomnia and those who are exposed to sleep deprivation, experience systematic sleep disturbance. For the purpose of this study, individuals with insomnia were considered to exhibit chronic sleep disturbance (diagnostic criteria is non-restorative sleep for ≥1 month) [21], while participants in experimental sleep deprivation studies are generally exposed to short-term sleep loss (e.g., ≤48 h). The differentiation between chronic and short-term sleep disturbance is important, as it is likely that there are different cognitive consequences [22]. Comparing and contrasting the cognitive profile of OSA with those of COPD, chronic insomnia, and short-term sleep deprivation (summarised in Table 1) could provide useful insights into the relative contributions of chronic and short-term sleep disturbance, and hypoxia/hypercarbia to the cognitive deficits observed in OSA.

Section snippets

Search

All review papers addressing the topic of cognitive function in OSA, COPD, insomnia, and sleep deprivation between 1st January 1980 and 12th January 2016 were examined. Systematic reviews and meta-analyses were included if they examined one or more of these conditions in adults and compared data with norms or controls before any treatment or intervention. Fig. 1 presents a summary of the search terms selected, databases searched, and numbers of papers included and excluded at each stage of the

Cognitive deficits in OSA

The search found two new papers reporting on cognition in adults before OSA treatment ∗[27], ∗[28] to add to the five papers [7], ∗[8], ∗[9], [10], ∗[11] reported in our 2012 meta-review on cognition in OSA [6] (see Online Supplement: Table 1). Inclusion of these two recent reviews into the current meta-review produced results consistent with the previous meta-review, which demonstrated that individuals with OSA had deficits in the domains of attention, executive function,

Discussion

The present paper used meta-review methodology to compare the cognitive profiles of individuals with OSA, COPD, insomnia, and those exposed to experimental sleep deprivation. Cognitive deficits were observed in OSA (attention, memory, executive function, psychomotor function, visuospatial/construction function and language function), COPD (attention, memory, executive function, psychomotor function, language function), and sleep deprivation (attention, memory, and general cognition), but not in

Conclusions

The present paper systematically analysed the overlaps in, and distinctions between, the cognitive profiles of people with OSA, insomnia, COPD, and sleep deprivation. This was undertaken to examine the basis for cognitive deficits in OSA including the potentially separable contributions of hypoxia/hypercarbia and sleep fragmentation, and to provide stimulus for future research.

Cognitive deficits shared by OSA and COPD (attention, memory, executive function, psychomotor function, and language

Conflicts of interest

The authors have no relevant conflicts of interest to report.

References (53)

  • R. Bucks et al.

    Neurocognitive function in obstructive sleep apnoea: a meta-review

    Respirology

    (2012)
  • S. Fulda et al.

    Cognitive dysfunction in sleep-related breathing disorders: a meta-analysis

    Sleep Res Online

    (2003)
  • D.W. Beebe et al.

    The neuropsychological effects of obstructive sleep apnea: a meta-analysis of norm-referenced and case-controlled data

    Sleep

    (2003)
  • A. Wallace et al.

    Memory and obstructive sleep apnoea: a meta-analysis

    Sleep

    (2012)
  • M.S. Aloia et al.

    Clinical management of poor adherence to CPAP: motivational enhancement

    Behav Sleep Med

    (2004)
  • T. Saunamäki et al.

    A review of executive functions in obstructive sleep apnea syndrome

    Acta Neurol Scand

    (2007)
  • D.W. Beebe

    Neurobehavioral effects of obstructive sleep apnea: an overview and heuristic model

    Curr Opin Pulm Med

    (2005)
  • D.W. Beebe et al.

    Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits

    J Sleep Res

    (2002)
  • M.S. Aloia et al.

    Neuropsychological sequelae of obstructive sleep apnea-hypopnea syndrome: a critical review

    J Int Neuropsychol Soc

    (2004)
  • M. Olaithe et al.

    Cognition and nocturnal disturbance in OSA: the importance of accounting for age and premorbid intelligence

    Sleep Breath

    (2015)
  • R. Weston et al.

    A brief guide to structural equation modeling

    Couns Psychol

    (2006)
  • T. Roehrs et al.

    Neuropsychological function in obstructive sleep apnea syndrome (OSAS) compared to chronic obstructive pulmonary disease (COPD)

    Sleep

    (1995)
  • S. Fulda et al.

    Cognitive dysfunction in sleep disorders

    Sleep Med Rev

    (2001)
  • G. Andreou et al.

    Effects of chronic obstructive pulmonary disease and obstructive sleep apnea on cognitive functions: evidence for a common nature

    Sleep Disord

    (2014)
  • D.M. Mannino et al.

    Global burden of COPD: risk factors, prevalence, and future trends

    Lancet

    (2007)
  • APA

    Diagnostic and statistical manual of mental disorders

  • Cited by (227)

    View all citing articles on Scopus

    The most important references are denoted by an asterisk.

    View full text